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Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse models
- Source :
- Life Science Alliance
- Publication Year :
- 2020
- Publisher :
- Life Science Alliance, LLC, 2020.
-
Abstract
- This study used mice heterozygous for Tp53 mutations with different genetic backgrounds to investigate the genetic or stochastic factors that modify the penetrance of tumor formation by Tp53 mutation.<br />p53 is the most frequently mutated gene in human cancers. Li-Fraumeni syndrome patients inheriting heterozygous p53 mutations often have a much-increased risk to develop cancer(s) at early ages. Recent studies suggest that some individuals inherited p53 mutations do not have the early onset or high frequency of cancers. These observations suggest that other genetic, environmental, immunological, epigenetic, or stochastic factors modify the penetrance of the cancerous mutant Tp53 phenotype. To test this possibility, this study explored dominant genetic modifiers of Tp53 mutations in heterozygous mice with different genetic backgrounds. Both genetic and stochastic effects upon tumor formation were observed in these mice. The genetic background of mice carrying Tp53 mutations has a strong influence upon the tissue type of the tumor produced and the number of tumors formed in a single mouse. The onset age of a tumor is correlated with the tissue type of that tumor, although identical tumor tissue types can occur at very different ages. These observations help to explain the great diversity of cancers in different Li-Fraumeni patients over lifetimes.
- Subjects :
- Male
0301 basic medicine
Heterozygote
endocrine system diseases
Carcinogenesis
Health, Toxicology and Mutagenesis
Mutant
Mice, Transgenic
Plant Science
Biology
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Li-Fraumeni Syndrome
Mice
03 medical and health sciences
0302 clinical medicine
stomatognathic system
Mice, Inbred NOD
medicine
Animals
Genetic Predisposition to Disease
Epigenetics
Li fraumeni
neoplasms
Gene
Germ-Line Mutation
Research Articles
Mice, Inbred BALB C
Stochastic Processes
Ecology
Cancer
medicine.disease
Phenotype
Penetrance
Tumor formation
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Mice, Inbred DBA
030220 oncology & carcinogenesis
Cancer research
Female
Tumor Suppressor Protein p53
Research Article
Subjects
Details
- ISSN :
- 25751077
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Life Science Alliance
- Accession number :
- edsair.doi.dedup.....898fd3faa5332cf6e5daa810607e9108